title: Evaluation of the structure-activity relationship of rifabutin and analogs: a drug-membrane study.
abstract: This work focuses on the influence of rifabutin and two novel analogs, namely, N'-acetyl-rifabutin and N'-butanoyl-rifabutin, on the biophysical properties of lipid membranes. Monolayers and multilamellar vesicles composed of egg L-α-phosphatidylcholine:cholesterol in a molar ratio of 4:1 are chosen to mimic biological membranes. Several accurate biophysical techniques are used to establish a putative relationship between the chemical structure of the antimycobacterial compounds and their activity on the membranes. A combination of in situ experimental techniques, such as Langmuir isotherms, Brewster angle microscopy, polarization-modulated infrared reflection-absorption spectroscopy, and small-angle X-ray scattering, is used to assess the drug-membrane interaction. A relationship between the effect of a drug on the organization of the membranes and their chemical structure is found and may be useful in the development of new drugs with higher efficacy and fewer toxic effects.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Pinheiro
authors.forename: Catarina
authors.initials: C
authors.lastname: Pereira-Leite
authors.forename: Mariana
authors.initials: M
authors.lastname: Arêde
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.forename: João M
authors.initials: JM
authors.lastname: Caio
authors.forename: Cristina
authors.initials: C
authors.lastname: Moiteiro
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Giner-Casares
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.forename: Luis
authors.initials: L
authors.lastname: Camacho
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D055119:Elastic Modulus; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry; D017828:Rifabutin / Q000031:analogs & derivatives*; D053838:Scattering, Small Angle; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D017828:Rifabutin; D002784:Cholesterol
keywords: antibiotics; monolayers; phospholipids; structure-activity relationships; vesicles